Sex-related patterns of functional brain networks in children and adolescents with autism spectrum disorder

Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7-18 years) and 86 typically developing controls (TCs) (43 females, aged 7-18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole-brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex-related differences in topological metrics using a 2 x 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus. In this study, we focused on sex-related alterations in the topological organization of functional networks in ASD and found greater differences between ASD and TCs in females than in males, consistent with the female protective effect hypothesis. Furthermore, the lack of neurotypical sex differences in ASD suggested that the processes of typical neural sex differentiation might be disturbed in ASD. These findings offer a fresh perspective on the sex differences of ASD at the large-scale network level.